chr8-61503457-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4BS1_Supporting
The NM_004318.4(ASPH):c.2179G>A(p.Val727Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000301 in 1,613,108 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_004318.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ASPH | ENST00000379454.9 | c.2179G>A | p.Val727Ile | missense_variant | Exon 25 of 25 | 1 | NM_004318.4 | ENSP00000368767.4 | ||
ASPH | ENST00000541428.5 | c.2092G>A | p.Val698Ile | missense_variant | Exon 25 of 25 | 2 | ENSP00000437864.1 |
Frequencies
GnomAD3 genomes AF: 0.000158 AC: 24AN: 152236Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000235 AC: 58AN: 247254Hom.: 1 AF XY: 0.000321 AC XY: 43AN XY: 133832
GnomAD4 exome AF: 0.000316 AC: 462AN: 1460754Hom.: 1 Cov.: 29 AF XY: 0.000337 AC XY: 245AN XY: 726654
GnomAD4 genome AF: 0.000158 AC: 24AN: 152354Hom.: 0 Cov.: 33 AF XY: 0.000134 AC XY: 10AN XY: 74502
ClinVar
Submissions by phenotype
not provided Uncertain:1
Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 727 of the ASPH protein (p.Val727Ile). This variant is present in population databases (rs147092046, gnomAD 0.05%), including at least one homozygous and/or hemizygous individual. This variant has not been reported in the literature in individuals affected with ASPH-related conditions. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at